Session: 901. Health Services and Quality Improvement: Non-Malignant Conditions Excluding Hemoglobinopathies: Poster II
Hematology Disease Topics & Pathways:
Clinical Practice (Health Services and Quality)
Methods: Data were based on initial safety signals being identified by a RADAR/SONAR co-investigator. Then, case-series were derived. Collaborations with basic scientists allowed for basic science correlative studies. Results were disseminated primarily as Brief Report in the literature and Black Box warnings on the related drug. In some instances, studies identified hematologic toxicities that prevent FDA from approving a submitted drug application.
Results: sADRs were frequently identified based on very small case series, including ticlopidine-and clopidogrel associated thrombotic thrombocytopenic purpura (22 and 10 patients, respectively), thalidomide- and lenalidomide-associated venous thromboembolism (9 and 5 patients, respectively), rituximab-associated progressive multi-focal leukoencephalopathy (22 patients), peginesatide-associated fatal anaphylaxis (5 patients), and COVID-19 vaccine associated immune thrombocytopenia (1 patient). Meta-analyses provided data for epoetin- and darbepoetin-associated mortality among cancer patients and lenalidomide- and thalidomide-associated venous thromboembolism. Following the onset of the COVID-19 pandemic, RADAR/SONAR investigated social media and pre-prints (COVID-19 vaccine associated cerebral vein thrombosis and immune thrombocytopenia). Time from FDA approval to sADR discovery was a median of 5 years (range, 0 months (thalidomide-associated venous thromboembolism) to 34 years (ciprofloxacin-associated neuropsychiatric toxicity). Basic science correlative studies identified ADAMTS13 autoantibodies (ticlopidine), leachates that developed in a multi-dose vial (peginesatide), anti-red blood cell antibodies (epoetin-associated pure red cell aplasia), and high-risk genes (fluoroquinolones and rituximab). Overall, RADAR/SONAR studies are estimated to have saved over 1 million lives and also resulted in overall payments to the Department of Justice of $1.5 billion (related to marketing of unsafe drugs).
Discussion: RADAR/SONAR has proven to be a very important adjunct to FDA and pharmaceutical manufacturer-led safety investigations for hematology, paralleling the success in medical oncology and in cardiology. Going forward, independent centers of excellence for safety-focused investigations such as the CERSI network and the SENTINEL network (both are NIH funded) should be broadened to include a hematology-focused safety center.
Disclosures: Thiruvengadam: Genentech: Research Funding; ADC-Therapeutics: Research Funding; Ipsen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genmab: Consultancy, Research Funding; Abbvie: Consultancy. Rosen: Astra Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees.